Andexanet alfa for reversal of factor Xa inhibitors: a critical review of the evidence

Direct oral anticoagulants are associated with lower rates of bleeding than vitamin K antagonists, but life-threatening bleeding still occurs. Andexanet alfa is a catalytically inactive recombinant modified human factor Xa molecule that reverses the anticoagulant effect of direct and indirect acting factor Xa inhibitors. In the ANNEXA-4 study, treatment with andexanet was associated with a 92% reduction in median anti-Xa activity levels and excellent or good hemostasis in 82% of patients presenting with serious bleeding while receiving apixaban or rivaroxaban. In this review, we discuss the burden of bleeding in anticoagulated patients and the need for reversal agents, review the mechanism of action of andexanet and critically evaluate the evidence for its efficacy and safety.